Acute Myeloid LeukemiaPhase 1NCT06197672
Chimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory Acute Myeloid Leukemia (AML ) as a Bridge to Allogeneic Stem Cell Transplant
A Phase 1 study testing CD4CAR in people with Acute Myeloid Leukemia, run by Huda Salman at 4 sites in United States.
Trial summary
This study is designed as a single arm open label traditional Phase I, 3+3, study of CD4-redirected chimeric antigen receptor engineered T-cells (CD4CAR) in subjects with relapsed or refractory AML. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- CD4CAR
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 4 sitesUnited States
- Study dates
- 19 Mar 2024to Dec 2042
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- ≥ 12 years old at the time of informed consent
- Ability to provide written informed consent and HIPAA authorization.
- Diagnosis of AML that is CD4+ and must have failed standard induction/ first line treatment such as intensive induction or less intensive hypomethylation and venetoclax first line. In the specific case of azacitidine and venetoclax (aza/ven), BM biopsy for response assessment on days 21-28 of first cycle. If disease progression by increasing number of blasts is documented, subject will be eligible. If no morphologic remission (persistent BM blasts above 5%) but evidence of efficacy exists, a second cycle without interruption will be given with the goal of achieving morphologic remission and repeat BM biopsy on days 21-28 of this cycle. If residual disease or disease progression is captured, then they will be considered refractory and will qualify for this trial. This is unless the subject now qualifies for a more intensive induction therapy that they did not qualify for when aza/ven was initially chosen as first-line treatment. Given the low response rate for aza/ven in the RR-AML, CR of only 13%, this combination would not be a prerequisite to qualify for the study.
- Note: If these subjects who fail first line treatment have an FDA approved treatment options available (including targeted and non-targeted treatment) for a second line treatment, they do not qualify for the trial until they also are deemed nonresponsive to those. If an approved second line is not available, subjects will be eligible after first line failure.
- Creatinine clearance of > 60ml/min (or otherwise non clinically significant, per study investigator)
- alanine aminotransferase/ aspartate aminotransferase ALT/AST < 3 x ULN
Show all 12Show fewer
- Bilirubin < 2 x ULN (UPPER LIMIT OF NORMAL)
- No supplemental oxygen at rest Note: Pulmonary Function Test (PFT) only required per treating physician discretion
- Adequate cardiac function with EJECTION FRACTION, EF, of ≥50%
- Adequate venous access for apheresis and no other contraindications for leukapheresis Note: Adequate venous access means either sufficient access to a peripheral vein for collection or if venous access is insufficient for standard access, subject must have the ability to receive a temporary central venous catheter to establish venous access for apheresis.
- Note: Any treatment being given prior to leukapheresis must be stopped at least 2-3 weeks prior to leukapheresis.
- Confirmation of a bone marrow donor for post CD4CAR transplant to proceed to transplant if eligible post treatment.
Who cannot join
- CD4 negative AML
- Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential (see definition below) must have a negative serum or urine pregnancy test prior to initiation of conditioning chemotherapy, per research sites' clinical policy.
- Uncontrolled active infection necessitating systemic therapy.
- Active hepatitis B hb, or hepatitis C, HC, infection. Active hepatitis C is defined as the hepatitis C antibody is positive while quantitative HCV RNA results exceed the lower detection limit.
- Note the following subjects will be eligible:
- Subjects with a history of hepatitis B but have received antiviral therapy and have non-detectable viral DNA for 6 months prior to enrollment are eligible.
Show all 40Show fewer
- Subjects seropositive for HBS antibodies due to hepatitis B virus vaccine with no signs or active infection (Negative HBs Ag, HBc and HBe Ags) are eligible.
- Subjects who had hepatitis C but have received antiviral therapy and show no detectable hepatitis C virus (HCV) viral RNA for 6 months are eligible.
- If hepatitis C antibody test is positive, then subjects must be tested for the presence of antigen by reverse transcription-polymerase chain reaction (RT-PCR) and be hepatitis C virus ribonucleic acid (HCV RNA) negative.
- Concurrent use of systemic glucocorticoids in greater than replacement doses or steroid dependency defined in rheumatological and pulmonary diseases as uninterrupted corticosteroid intake for more than a year at a dosage of 0.3 mg/kg/day or greater, and where the underlying disease worsens on temporary stoppage of steroid therapy, with symptoms of steroids withdrawal (e.g., lethargy, headache, weakness, pseudo rheumatism, emotional disturbances, etc) precipitated by the temporary stoppage unless tapering can occur safely without compromising the underlying disease, the withdrawal tolerance and can happen in a timeframe appropriate to enroll in this trial without safety concerns
- Subjects who receive daily corticosteroids in replacement doses can be included in the study. The replacement doses are defined as following:
- Hydrocortisone 25mg/day or less
- Prednisone 10mg/day or less
- Dexamethasone 4mg or less Note: Recent or current use of inhaled glucocorticoids is not exclusionary, as this route pertains extremely minimal systemic penetration
- Any uncontrolled active medical disorder that would preclude participation as outlined in the opinion of the treating investigator and/or Principal Investigator
- HIV infection
- Subjects who have received or will receive live vaccines within 30 days before the first experimental cell treatment. Inactivated seasonal flu vaccination is allowed.
- Subjects with active autoimmune diseases who need systematic treatments (such as disease modifying agents, corticosteroids, and immunosuppressive drugs) during the last year.
- Note: Replacement therapy (thyroxine, insulin, or physiological corticosteroid replacement therapy (up to10 mg of oral daily prednisone or equivalent in hydrocortisone and dexamethasone) to treat adrenal dysfunction or pituitary dysfunction) is not considered as systematic therapy. Subjects who need inhalation corticosteroid therapy can be included in this trial. Subjects with vitiligo or in long-term remission of pediatric asthma or allergic diseases can be included in this trial.
- Subjects with a history of mental disorders or drug abuse that may influence treatment compliance.
- Active malignancy not related to AML that has required therapy in the last 3 years or is not in complete remission. Exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy. Other similar malignant conditions may be discussed with and permitted by the Principal Investigator.
- Treatment with any investigational cell/gene therapy within the past 6 months
- Treatment with any investigational anticancer agent within the past 14 days of study entry or 5 half-lives (whichever is shorter).
- Eligibility for Conditioning Chemotherapy:
- Specific organ function criteria for cardiac, renal, and liver function must be similar to initial inclusion values.
- Review of co-morbidities to confirm no major changes in health status (examples of major changes include heart attack, stroke, and any major trauma).
- Planned infusion does was successfully manufactured and met release criteria.
- Negative pregnancy testing (if applicable).
- Eligibility for CD4CAR infusion:
- Afebrile and not receiving antipyretics, and no evidence of active infection per PI discretion. If fever is attributed to underlying disease, it will not disqualify.
- Specific organ function criteria for cardiac, renal, and liver function must be similar to initial inclusion values. The following tests does not need repeated: EF if within 6 weeks of screening assessment.
- Note: Subjects may require a repeat PFT prior to CD4CAR infusion as determined by the treating physician in the following possible cases:
- Subject develops a respiratory infection that results in significant changes in lung imaging from baseline
- Subject's oxygenation from daily activities is compromised at baseline; or there is a significant change in oxygenation or lung imaging from baseline
- If previous history of corticosteroid chemotherapy, subject must be off all but adrenal replacement doses 3 days before the CD4CAR infusion.
- Note: A subject may still receive the CD4CAR infusion up to 10 days post conditioning chemotherapy as long as they do not meet any of the following at time of infusion:
- Requirement for supplemental oxygen to keep saturation greater than 95% or presence of radiographic abnormalities on a clinically indicated chest x-ray that are progressive.
- New cardiac arrhythmia not controlled with medical management.
- Hypotension requiring pressor support.
- Positive blood cultures for bacteria, fungus, or virus within 48-hours of T cell infusion.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, 46202
Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
About this study
Official title: Chimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory AML as a Bridge to Allogeneic Stem Cell Transplant
This study is designed as a single arm open label traditional Phase I, 3+3, study of CD4-redirected chimeric antigen receptor engineered T-cells (CD4CAR) in subjects with relapsed or refractory AML. The study will evaluate safety in this subject population and also the presence of efficacy signal described by elimination of residual disease to qualify subjects for stem cell transplant.
Read the detailed description
The study will be performed as a dose-escalation protocol. The investigators expect to recruit 20 subjects at Indiana University with an expected dropout rate of 25% primarily due to rapid progression or death and screen and or manufacturing failure. Taking this into account, the investigators expect to treat 15 subjects. The study will utilize autologous CD4CAR T-cells that are engineered to express a chimeric antigen receptor (CAR) targeting CD4 that is linked to the cluster of differentiation 28 (CD28), 4-1BB, cluster of differentiation 3-zeta (CD3ζ) signaling chains (third generation CAR). about 70% of AML with monocytic differentiation and 37% of all the rest express CD4 on their blasts.
At entry, disease status will be assessed. Qualifying subjects will be leukapheresed to obtain large numbers of peripheral blood mononuclear cells (PBMC) for the manufacturing. Then, participants will receive conditioning chemotherapy. Next, participants will receive CD4CAR cells by infusion on Day 0 of treatment. (The initial dose for this trial will be the highest dose level that was deemed safe from our other ongoing trials by the time this trial is ready to accrue).
If the disease progresses during the manufacturing period participants may be excluded from the study or an attempt to bridge for disease control will be offered. Minimal chemotherapy to keep the disease under control in the meanwhile is allowed if deemed necessary by investigators.
A single dose of CD4CAR transduced T cells will consist of the cell number for the dose level to be infused.
Post-infusion monitoring of CD4CAR T-cells: Subjects will have blood drawn for cytokine levels, CD4CAR Transgene Copy Number (PCR) and flow cytometry in order to evaluate the presence of CD4CAR cells on days 0, 1, 3, 5, 7, 14, and 28 following infusion (or as clinically needed). Cytokines levels will be evaluated per schedule above in addition to and as needed every 8 +/- 2 hours as feasible if/when Cytokine Release Syndrome, CRS, occurs and until resolution. Active monitoring of fungal and viral infections during treatment while utilizing standard prophylaxis recommended for HIV-positive subjects with T-cell aplasia and those undergoing allogeneic stem cell transplant. Investigators plan to collect data about clinicoradiologic measurements of residual tumor burden starting on day 7 and weekly afterward until Day 28 and then monthly for 6 months. This will be followed by quarterly clinical evaluations for the next two (2) years with a medical history, physical examination, and comprehensive blood testing. After these short- and intermediate-term evaluations are performed, these subjects will enter a rollover study to assess for disease-free survival (DFS), relapse, and the development of other health problems or malignancies where follow-up will be up to twice a year by phone and a questionnaire for an additional thirteen (13) years. The treating physician will decide to proceed with allogeneic or autologous transplant when needed.
Dose of CD4CAR description: the main objective of this study is to establish a recommended dose and/or schedule of CD4CAR. The guiding principle for dose escalation in phase I is to avoid unnecessary exposure of subjects to sub-therapeutic doses (i.e., to treat as many subjects as possible within the therapeutic dose range) while preserving safety and maintaining rapid accrual. Investigators will use the rule-based traditional Phase I "3+3" design for the evaluation of safety. Based on lab experience in mice the starting dose (dose level 1) for the first cohort of three subjects in phase I portion of the study will be 8x10^5 cells. The dose escalation or de-escalation will follow a modified Fibonacci sequence as below.
If more than one subject out of the first cohort of three subjects in dose level 1 experience dose limiting toxicity (DLT), the trial will be placed on hold. If zero or one out of three subjects in the first cohort of dose level 1 experience DLT, three more subjects will be enrolled at dose level 1; the dose escalation continues until at least two subjects among a cohort of six subjects experience DLT (i.e., ≥33% of subjects with a DLT at this dose level)
If one of the first three subjects in dose level 1 experiences a DLT, three more subjects will be treated at dose level 1.
If none of the three subjects or only one of the 6 subjects in the dose level 1 experiences a DLT, the dose escalation continues to the dose level 2 If one of the first three subjects in dose level 2 experience a DLT, three more subjects will be treated at dose level 2 If none of the three subjects or only one of the 6 subjects in the dose level2 experiences a DLT, the dose escalation continues to the dose level 3 If one of the first three subjects in dose level 3 experiences a DLT, three more subjects will be treated at dose level 3 If none of the three subjects or only one of the 6 subjects in the dose level 3 experiences a DLT, dose level 3 will be declared the maximum tolerated dose (MTD) and will be used as the recommended phase II dose (RP2D) for the phase II portion of the study.
In summary, the dose escalation continues until at least two subjects among a cohort of six subjects experience DLT (i.e., ≥33% of subjects with a DLT at that dose level). The recommended dose for phase II trials is defined as one dose level below this toxic dose level. Since some grade 3 and possibly 4 toxicities are highly likely to be reversible, grade 3 infectious, hematological and vascular toxicities will not be considered DLTs mandating dose reduction. Also allergic or infusion-related reactions ≤ grade 3 will not be counted as DLTs. There will be no intra-subject dose escalation or reduction.
To allow for full spectrum toxicity duration evaluation and reporting, no subjects within the same or a different cohort will be initiated on lymphodepleting chemotherapy sooner than 28 days from the initiation date of the preceding subject.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- CD4CAR
- Keywords
- Acute Myeloid Leukemia, T Cell, Cell Therapy, CAR T, Chimeric Antigen Receptor Therapy
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD4CARBiological
CD4CAR cells transduced with a lentiviral vector to express the single-chain variable fragment (scFv) nucleotide sequence of the anti-CD4 molecule derived from humanized monoclonal ibalizumab and the intracellular domains of CD28 and 4-1BB co-activators fused to the CD3ζ T-cell activation signaling domain administered by IV infusions as a single dose
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Redirected autologous T cells transduced with the anti-CD4 lentiviral vector (referred to as "CD4CAR" cells) Receives: Biological: CD4CAR |
What is being measured
The primary outcome is the main question the study is designed to answer.
1. Dose finding: Maximum tolerated dose (MTD) is defined as one dose level lower than the Dose Limiting Toxicity (DLT) of the CD4CAR in AML. Optimal dose is highest safe dose that produces the most response.
In this traditional phase 1 dose escalation, cohorts of three subjects will be treated on a dose level that will be incremented to next dose level if no dose limiting toxicities (DLT) were reported or expanded if a DLT is documented.
Measured: Day 0 through Day 28 post-infusion
Persistence and biologic behavior of CD4CAR as measured by a. Serial blood and marrow sampling to detect CD4CAR over time post infusion. b. Serial testing for CD4CAR proliferation, differentiation and polarization if feasible overtime after infusion.
The persistence of the CAR through day 28 and possibly longer if detected by D28. This will be performed by flow to assess for the CD3+/Fab2+ cell population The phenotype of the CAR will be determined by flow as well, to look for Tcm phenotype
Measured: Day 0 Through Day28 post infusion
3. Determine the influence of CD4CAR on T regs
- Examine the efficacy of CD4CAR on changing the frequency of T regs subpopulation after CD4CAR infusion as compared to their frequency prior to treatment.
- Determine the impact of the change in T regs and MDSCs abundance on objective response to CD4CAR.
Measured: Day 0 through Day 28
Determine the influence of CD4CAR on myeloiod derived suppressor cells, MDSCs
Examine the efficacy of CD4CAR on changing the frequency of MDSCs subpopulation
Measured: Day 0 through Day 28
Secondary outcomes (3)
Determine mLSCs frequency before and after the CD4CAR infusion
Participants' blood will be tested by flow cytometry to determine the ability of CD4CAR to target Monocytic Leukemia Stem Cells (mLSCs).
Measured: Baseline through Day 30
Quantification of CD4CAR associated cytokines
Participants blood will be examined for cytokine level changes according to time points as described in the protocol.
Measured: Baseline through Day 30
Describe disease response using European LeukemiaNet (ELN) 2022 recommendation
Treatment is intended to reduce the disease burden enough to qualify subjects for stem cell transplant through either elimination of residual disease or minimizing that to being acceptable to transplant consideration. For response evaluation of the frequency of successful bridging to transplant, European LeukemiaNet (ELN) 2022 recommendation will be applied.
Measured: Baseline through Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2024
- Study start19 Mar 2024
- Primary completionDec 2027 (estimated)
- Study completionDec 2042 (estimated)
Why it stopped: Trial being transferred to new lead site
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Huda Salman
- Sponsor type
- University, hospital or other
- Collaborators
- iCell Gene Therapeutics
- Responsible party
- Sponsor-investigator, Huda Salman, Indiana University
- Investigators
- Jennifer Schwartz, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06197672
- Sponsor's protocol ID
- CTO-IUSCCC-0851
- Status last verified
- Sep 2026
- First submitted
- 14 Dec 2023
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory AML as a Bridge to Allogeneic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT06197672
- Acronym / sponsor ID
- CTO-IUSCCC-0851
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Acute Myeloid Leukemia, T Cell, Cell Therapy, CAR T, Chimeric Antigen Receptor Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Trial being transferred to new lead site
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Huda SalmanUniversity, hospital or other
- Collaborators
- iCell Gene Therapeutics
- Study start
- 19 Mar 2024 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2042 (estimated)
- First posted
- 9 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed as a single arm open label traditional Phase I, 3+3, study of CD4-redirected chimeric antigen receptor engineered T-cells (CD4CAR) in subjects with relapsed or refractory AML. The study will evaluate safety in this subject population and also the presence of efficacy signal described by elimination of residual disease to qualify subjects for stem cell transplant.
Detailed description
The study will be performed as a dose-escalation protocol. The investigators expect to recruit 20 subjects at Indiana University with an expected dropout rate of 25% primarily due to rapid progression or death and screen and or manufacturing failure. Taking this into account, the investigators expect to treat 15 subjects. The study will utilize autologous CD4CAR T-cells that are engineered to express a chimeric antigen receptor (CAR) targeting CD4 that is linked to the cluster of differentiation 28 (CD28), 4-1BB, cluster of differentiation 3-zeta (CD3ζ) signaling chains (third generation CAR). about 70% of AML with monocytic differentiation and 37% of all the rest express CD4 on their blasts.
At entry, disease status will be assessed. Qualifying subjects will be leukapheresed to obtain large numbers of peripheral blood mononuclear cells (PBMC) for the manufacturing. Then, participants will receive conditioning chemotherapy. Next, participants will receive CD4CAR cells by infusion on Day 0 of treatment. (The initial dose for this trial will be the highest dose level that was deemed safe from our other ongoing trials by the time this trial is ready to accrue).
If the disease progresses during the manufacturing period participants may be excluded from the study or an attempt to bridge for disease control will be offered. Minimal chemotherapy to keep the disease under control in the meanwhile is allowed if deemed necessary by investigators.
A single dose of CD4CAR transduced T cells will consist of the cell number for the dose level to be infused.
Post-infusion monitoring of CD4CAR T-cells: Subjects will have blood drawn for cytokine levels, CD4CAR Transgene Copy Number (PCR) and flow cytometry in order to evaluate the presence of CD4CAR cells on days 0, 1, 3, 5, 7, 14, and 28 following infusion (or as clinically needed). Cytokines levels will be evaluated per schedule above in addition to and as needed every 8 +/- 2 hours as feasible if/when Cytokine Release Syndrome, CRS, occurs and until resolution. Active monitoring of fungal and viral infections during treatment while utilizing standard prophylaxis recommended for HIV-positive subjects with T-cell aplasia and those undergoing allogeneic stem cell transplant. Investigators plan to collect data about clinicoradiologic measurements of residual tumor burden starting on day 7 and weekly afterward until Day 28 and then monthly for 6 months. This will be followed by quarterly clinical evaluations for the next two (2) years with a medical history, physical examination, and comprehensive blood testing. After these short- and intermediate-term evaluations are performed, these subjects will enter a rollover study to assess for disease-free survival (DFS), relapse, and the development of other health problems or malignancies where follow-up will be up to twice a year by phone and a questionnaire for an additional thirteen (13) years. The treating physician will decide to proceed with allogeneic or autologous transplant when needed.
Dose of CD4CAR description: the main objective of this study is to establish a recommended dose and/or schedule of CD4CAR. The guiding principle for dose escalation in phase I is to avoid unnecessary exposure of subjects to sub-therapeutic doses (i.e., to treat as many subjects as possible within the therapeutic dose range) while preserving safety and maintaining rapid accrual. Investigators will use the rule-based traditional Phase I "3+3" design for the evaluation of safety. Based on lab experience in mice the starting dose (dose level 1) for the first cohort of three subjects in phase I portion of the study will be 8x10^5 cells. The dose escalation or de-escalation will follow a modified Fibonacci sequence as below.
If more than one subject out of the first cohort of three subjects in dose level 1 experience dose limiting toxicity (DLT), the trial will be placed on hold. If zero or one out of three subjects in the first cohort of dose level 1 experience DLT, three more subjects will be enrolled at dose level 1; the dose escalation continues until at least two subjects among a cohort of six subjects experience DLT (i.e., ≥33% of subjects with a DLT at this dose level)
If one of the first three subjects in dose level 1 experiences a DLT, three more subjects will be treated at dose level 1.
If none of the three subjects or only one of the 6 subjects in the dose level 1 experiences a DLT, the dose escalation continues to the dose level 2 If one of the first three subjects in dose level 2 experience a DLT, three more subjects will be treated at dose level 2 If none of the three subjects or only one of the 6 subjects in the dose level2 experiences a DLT, the dose escalation continues to the dose level 3 If one of the first three subjects in dose level 3 experiences a DLT, three more subjects will be treated at dose level 3 If none of the three subjects or only one of the 6 subjects in the dose level 3 experiences a DLT, dose level 3 will be declared the maximum tolerated dose (MTD) and will be used as the recommended phase II dose (RP2D) for the phase II portion of the study.
In summary, the dose escalation continues until at least two subjects among a cohort of six subjects experience DLT (i.e., ≥33% of subjects with a DLT at that dose level). The recommended dose for phase II trials is defined as one dose level below this toxic dose level. Since some grade 3 and possibly 4 toxicities are highly likely to be reversible, grade 3 infectious, hematological and vascular toxicities will not be considered DLTs mandating dose reduction. Also allergic or infusion-related reactions ≤ grade 3 will not be counted as DLTs. There will be no intra-subject dose escalation or reduction.
To allow for full spectrum toxicity duration evaluation and reporting, no subjects within the same or a different cohort will be initiated on lymphodepleting chemotherapy sooner than 28 days from the initiation date of the preceding subject.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Biological: CD4CARRedirected autologous T cells transduced with the anti-CD4 lentiviral vector (referred to as "CD4CAR" cells) |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- ≥ 12 years old at the time of informed consent
- Ability to provide written informed consent and HIPAA authorization.
- Diagnosis of AML that is CD4+ and must have failed standard induction/ first line treatment such as intensive induction or less intensive hypomethylation and venetoclax first line. In the specific case of azacitidine and venetoclax (aza/ven), BM biopsy for response assessment on days 21-28 of first cycle. If disease progression by increasing number of blasts is documented, subject will be eligible. If no morphologic remission (persistent BM blasts above 5%) but evidence of efficacy exists, a second cycle without interruption will be given with the goal of achieving morphologic remission and repeat BM biopsy on days 21-28 of this cycle. If residual disease or disease progression is captured, then they will be considered refractory and will qualify for this trial. This is unless the subject now qualifies for a more intensive induction therapy that they did not qualify for when aza/ven was initially chosen as first-line treatment. Given the low response rate for aza/ven in the RR-AML, CR of only 13%, this combination would not be a prerequisite to qualify for the study.
- Note: If these subjects who fail first line treatment have an FDA approved treatment options available (including targeted and non-targeted treatment) for a second line treatment, they do not qualify for the trial until they also are deemed nonresponsive to those. If an approved second line is not available, subjects will be eligible after first line failure.
- Creatinine clearance of > 60ml/min (or otherwise non clinically significant, per study investigator)
Key exclusion criteria (40 listed)
- CD4 negative AML
- Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential (see definition below) must have a negative serum or urine pregnancy test prior to initiation of conditioning chemotherapy, per research sites' clinical policy.
- Uncontrolled active infection necessitating systemic therapy.
- Active hepatitis B hb, or hepatitis C, HC, infection. Active hepatitis C is defined as the hepatitis C antibody is positive while quantitative HCV RNA results exceed the lower detection limit.
- Concurrent use of systemic glucocorticoids in greater than replacement doses or steroid dependency defined in rheumatological and pulmonary diseases as uninterrupted corticosteroid intake for more than a year at a dosage of 0.3 mg/kg/day or greater, and where the underlying disease worsens on temporary stoppage of steroid therapy, with symptoms of steroids withdrawal (e.g., lethargy, headache, weakness, pseudo rheumatism, emotional disturbances, etc) precipitated by the temporary stoppage unless tapering can occur safely without compromising the underlying disease, the withdrawal tolerance and can happen in a timeframe appropriate to enroll in this trial without safety concerns
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD4CARCD4CAR cells transduced with a lentiviral vector to express the single-chain variable fragment (scFv) nucleotide sequence of the anti-CD4 molecule derived from humanized monoclonal ibalizumab and the intracellular domains of CD28 and 4-1BB co-activators fused to the CD3ζ T-cell activation signaling domain administered by IV infusions as a single dose | Biological | Treatment |
Primary outcome
1. Dose finding: Maximum tolerated dose (MTD) is defined as one dose level lower than the Dose Limiting Toxicity (DLT) of the CD4CAR in AML. Optimal dose is highest safe dose that produces the most response.
Time frame: Day 0 through Day 28 post-infusion
In this traditional phase 1 dose escalation, cohorts of three subjects will be treated on a dose level that will be incremented to next dose level if no dose limiting toxicities (DLT) were reported or expanded if a DLT is documented.
Persistence and biologic behavior of CD4CAR as measured by a. Serial blood and marrow sampling to detect CD4CAR over time post infusion. b. Serial testing for CD4CAR proliferation, differentiation and polarization if feasible overtime after infusion.
Time frame: Day 0 Through Day28 post infusion
The persistence of the CAR through day 28 and possibly longer if detected by D28. This will be performed by flow to assess for the CD3+/Fab2+ cell population The phenotype of the CAR will be determined by flow as well, to look for Tcm phenotype
3. Determine the influence of CD4CAR on T regs
Time frame: Day 0 through Day 28
1. Examine the efficacy of CD4CAR on changing the frequency of T regs subpopulation after CD4CAR infusion as compared to their frequency prior to treatment. 2. Determine the impact of the change in T regs and MDSCs abundance on objective response to CD4CAR.
Determine the influence of CD4CAR on myeloiod derived suppressor cells, MDSCs
Time frame: Day 0 through Day 28
Examine the efficacy of CD4CAR on changing the frequency of MDSCs subpopulation
3 secondary outcomes
Determine mLSCs frequency before and after the CD4CAR infusion
Time frame: Baseline through Day 30
Quantification of CD4CAR associated cytokines
Time frame: Baseline through Day 30
Describe disease response using European LeukemiaNet (ELN) 2022 recommendation
Time frame: Baseline through Day 30
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
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MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
RecruitingPhase 1
225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody With Fludarabine, Melphalan and Total Marrow and Lymphoid Irradiation as Conditioning Treatment for Donor Stem Cell Transplant in Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
RecruitingPhase 2
Testing the Addition of Venetoclax or Gemtuzumab Ozogamicin (GO) to Usual Treatment Regimen (Cytarabine and Daunorubicin, "7+3") for Core Binding Factor Acute Myeloid Leukemia (CBF-AML) to Improve Response (A MYELOMATCH Treatment Trial)
Core Binding Factor Acute Myeloid Leukemia
RecruitingPhase 1/2
Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT)
Acute Myeloid Leukemia, Acute Lymphoid Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer Schwartz, MD principal investigator
Indiana University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD4CAR in people with Acute Myeloid Leukemia, run by Huda Salman at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1. Dose finding: Maximum tolerated dose (MTD) is defined as one dose level lower than the Dose Limiting Toxicity (DLT) of the CD4CAR in AML. Optimal dose is highest safe dose that produces the most response. (time frame: Day 0 through Day 28 post-infusion). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2026.